The goal of this FIRCA application is to develop and evaluate a new and direct assay of small airway function. In 1967 Macklem and Mead introduced the notion of the 'silent zone' of the lung, those small airways of the lung periphery in which airways disease can progress undetected because they contribute little to total pulmonary resistance. To this day the detection and quantification of small airway function is at best a process that is indirect, inferential and nonspecific. This application deals with an innovative animal model which adapts alveolar capsule technology to that important question. On the basis of preliminary studies, the sensitivity and specificity of this approach appear to make it by far the best method available to investigate small airway function in situ. The parent grant, a program project, deals with the cascade of events that culminate in normal or abnormal pulmonary architecture, mechanics and gas transport. The broader goal of this application is to foster deeper scientific collaboration between our respective laboratories in Boston and Szeged. The research aims of our two laboratories run very much in parallel, and the methods employed are very much complementary. As such it was natural for a collaborative exchange to arise spontaneously, just as it has. This collaboration began a little more than one year ago. One joint paper is in press and additional collaborative studies are underway. The factors limiting the current level of collaborative activity are resources for travel and the availability of equipment and reagents. The longer term potential for growth of this mutually beneficial enterprise is entirely dependent upon the availability of resources such as those requested in this application.